Best Practices: Evolving Understanding of Molecular Diagnostics and Biomarkers in Lung Cancer

At ASCO 2018, Oncology Practice Management (OPM) discussed the current state of genetics and genomic testing, the increasing understanding of biomarkers, and how they influence the treatment of patients with lung cancer. The discussion highlighted the interaction between oncologists and pathologists to facilitate best outcomes for patients. This interview included Lauren Ritterhouse, MD, PhD, Co-Director, Clinical Genomics Lab, University of Chicago, IL, and Geoff Oxnard, MD, Thoracic Oncologist, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School, Boston, MA.

OPM: The discovery of molecular biomarkers has made a significant impact on cancer treatment. How has this influenced your practice as an oncologist, Dr Oxnard, and your practice as a pathologist, Dr Ritterhouse?

Geoff Oxnard, MD: Over the past 10 years, lung cancer, specifically non–small-cell lung cancer (NSCLC), has witnessed a movement from empiric therapy, giving whatever drug to everyone, toward precision therapy, where we need answers to make informed and effective decisions for our patients.

Today, I generally tell my patients we have 3 broad tools—oral targeted therapies, immunotherapies, and chemotherapies. Before I start treatment, I need to know if the patient has a targetable genotype, such as EGFR or ALK. I also need to know if the cancer is sensitive or vulnerable to immunotherapy with a PD-L1 inhibitor.

If the evidence is not compelling that one of those therapies is going to work, I will begin with chemotherapy. At each decision point I need these data to make an informed decision.

Lauren Ritterhouse, MD, PhD: I run our molecular diagnostics lab, where we’re constantly thinking about new biomarkers that we need to incorporate into the lab, to be ahead of the curve. For example, if a new biomarker is released in a clinical trial, that’s the time for us to develop that new test in-house and find validation samples. It’s trying to think ahead what our oncologists will need to take care of patients.

The field is changing so rapidly. Every couple of months we have a message from an oncologist saying, “We need this on your panel, or we need this test.” We try to be on the edge of things and figure out what is the best for us to launch in the lab.

OPM: So, is it the pathologist who initiates a new biomarker to be included on a panel that you then recommend to the oncologist, or are the oncologists the ones who stay up to date on the latest biomarkers and recommend them to the pathologist?

Dr Oxnard: As oncologists, we first see the need for these questions answered for our patients. The biomarkers come to the forefront for us, and we reach out to the pathology lab to say, “I need this answered. You should be offering this for us.”

I work closely with our pathologists at Dana-Farber Women’s Hospital, who often say they only have so much bandwidth. We can only do so many tests effectively and cost-effectively. If you sign up for too many, you get stretched thin and you do them slowly. We need to have some balance. They’ll tell me which one we could have and when. We need a lot of interplay between the oncologist and the pathologists to figure out the right biomarker regimen for our site and for our patients.

Dr Ritterhouse: We work very closely with our oncologist groups. If a new drug targets a specific biomarker and shows good responses, we’ll have many requests to test for this biomarker. The request comes from the oncologists, and it’s helpful to have those conversations. Considering the limited resources, it’s important to have close working relationships to figure out exactly what’s the best use of all this information for the lab to develop. We’re both in academic settings. We do a lot of research that may be useful in the clinical setting in the future.

Dr Oxnard: We currently are hearing about new and potent RET inhibitors. Right now, we have a new biomarker every couple of months. The way we are managing at our site is a little different, but it is relevant to the ­individual patient.

In our daily interplay, I ask the pathologist, “When am I getting this back?” And the pathologist says, “How should I prioritize?” Because in the moment-to-moment decision-making, getting answers to questions about turnaround time and efficiency is important for my patients. This requires a lot of collaboration.

OPM: When does this discussion between the oncologist and the pathologist occur whether biomarker testing is appropriate for a particular patient?

Dr Ritterhouse: For our patients with lung cancer, it’s fairly streamlined and straightforward. Our surgical pathologist, molecular pathologists, and oncologists decided to delegate the ordering of molecular tests to the surgical pathologist for all patients with NSCLC. This way, the minute you get the biopsy and it’s adequate for molecular testing, the orders can be placed to reduce the time lag.

Dr Oxnard: We don’t have that in our clinic. Our pathologist still waits for the oncologist to order the test. Having that consensus to make a decision together is very important.

Dr Ritterhouse: For most lab tests, the clinicians place the order. It was indeed a shift in who is placing these orders, but it’s worked nicely. At a care facility like ours, some of our patients are coming in and their test material is at a different institution.

We put in the request so that the pathologist can review the material. Sometimes the pathologist gets the material before the patient has been seen by the oncologist to start the wheel moving. For immunohistochemistry (IHC) testing and molecular testing, as soon as they get a diagnosis of NSCLC, that order is started.

Anything that would be different from the routine care that’s been agreed on by everyone would probably be decided at tumor board, personal conversation, or by an e-mail saying, “I know we don’t normally do this....” Recently, I had a patient with small-cell lung cancer, and someone wanted us to run our next-generation sequencing (NGS) panel and do PD-L1 staining, although that’s not what we usually do. That was just a personal communication. We try to streamline the process to reduce turnaround time.

Dr Oxnard: Tumor boards are a very important forum, where we can expect to have the pathologist and the oncologist present, and sometimes other people. Everyone needs to look at a case together and think about the data and about what’s changing. The formal sit-down where we all think together and say, “What are we going to do about this?” is not the common event.

When we need a plan for a new biomarker, we all come together. When everyone sees that we have a challenge, we need to make a plan. It does require the oncologist who wants the answer, the surgical pathologist who handles the specimen, and the pathologist who will produce the test. They are the key people. Surgeons are often involved, and interventional radiologists are also important regarding tissue handling and tissue stewarding.

Dr Ritterhouse: In working on specimen adequacy in these multidisciplinary teams, we’ve worked closely with our interventional radiologists. Close to 80% of our lung cancer testing is done off of site-of-smear specimens from endobronchial ultrasound procedures. That was a big multidisciplinary group effort to streamline the testing of patients with lung cancer that’s been very successful and required many people coming to the table.

Dr Oxnard: We’re trying to do that more. We, and many other groups, are using the electronic medical record (EMR) system to increasingly structure our communications with interventional radiology or pathology. I order the biopsy and say, “Multiple cores. I want genomics. Please get a fine-needle aspiration, so I can have a smear for testing as well.” Not all EMR systems are flexible enough to allow that, but increasingly we all try to have the EMRs capture the key features so that those on the other side know what we mean.

OPM: As a pathologist, how do you ensure the accurate and producible measurement of PD-1/PD-L1? How do you report the results to the oncologist?

Dr Ritterhouse: At our site, PD-L1 testing is done routinely on all patients with NSCLC. As soon as the diagnosis is made that it’s NSCLC, then an IHC is ordered. It gets incorporated usually into the original pathology report of the biopsy or specimen.

Dr Oxnard: Along with the standard IHC results?

Dr Ritterhouse: Yes. Very rarely, if there’s a delay, it may be reported as an addendum, but usually it’s reported in the initial workup of the biopsy.

Dr Oxnard: This has become so fundamental that it has almost stopped being a molecular test and has become a routine IHC test that every patient with NSCLC has. Instead of being an extra order, the pathologist increasingly can just take care of it for the oncologist.

OPM: This is done only for lung cancer, correct?

Dr Ritterhouse: PD-1 IHC is evolving and is a standard test for all patients with NSCLC. If the oncologist is interested in another tumor type, that will require a personal communication. We just had a conversation with our oncologists who treat patients with mesothelioma, for example. Now we’re routinely ordering the test for all mesotheliomas, just like for NSCLC.

Dr Oxnard: We also think about it with small-cell lung cancer. We’re trying to use it more. PD-1 is an imperfect biomarker. When we have complicated decisions, every little data point can help.

Dr Ritterhouse: Those are things that we do on an ad-hoc basis on different tumor types. Again, it takes a communication to add the test. Things are evolving; if it’s becoming more important in other tumor types, our practice will evolve with it. PD-1 is not a perfect biomarker. There are discrepancies between different labs and the people interpreting the results.

We try to standardize the test and make it as robust as possible, so that the test that we perform can be validated against an external assay. Our thoracic pathologist either signs out all of them or she reviews someone else’s. It’s limited to 1 person always reviewing and reporting it, to ensure consistency.

Once it’s reported, it appears in the main pathology report as a percentage only, and the pattern of staining is reported. Then comes the interpretation, and at that point, the oncologist decides how to use the information.

OPM: How do the PD-1 or PD-L1 testing results influence your treatment plans?

Dr Oxnard: I use PD-L1 testing at the initial presentation of a patient with advanced lung cancer. If the testing results show more than 50% PD-L1 expression, it is a great opportunity for response to a single-agent immunotherapy. The opportunity to use immunotherapy alone, without the additional toxicities of combination therapies and without chemotherapy is very compelling. When it is less than 50% PD-L1 expression, I may consider chemotherapy or chemotherapy plus immunotherapy. Incorporating immunotherapy early on may improve overall survival.We’re looking for ways to use combination immunotherapies because of the potential for durable and dramatic response.

Quantifying PD-L1 expression gives us more information. We know that the higher the PD-L1 expression, the more likely the patient is to benefit from a single-agent immunotherapy. Based on recent data, regardless of whether the newly diagnosed advanced NSCLC is squamous or nonsquamous, if the PD-L1 is more than 50%, I can use single-agent immunotherapy and the patient has a good chance of response, and with reduced toxicity. If it is less than 50%, I will consider chemotherapy alone or with immunotherapy. We’re developing better combination immunotherapies and better biomarkers. PD-L1 doesn’t stand on its own. I use PD-L1 staining plus the patient’s clinical features, including a smoking history; genomic features, such as an EGFR or ALK mutation; and the presence of high tumor mutational burden (TMB). I use these details to decide if the patient is likely to benefit from a specific treatment.

OPM: Who drives the discussion about additional biomarker testing, such as TMB, microsatellite instability, and comprehensive genomic profiling?

Dr Oxnard: PD-L1 testing is now being done routinely for patients with NSCLC. When I see the patient in clinic, I have to consider whether the patient has a mutation such as EGFR, ALK, ROS1, RET, BRAF, or HER2.

I now routinely order NGS for patients with advanced nonsquamous NSCLC and for never smokers. I usually don’t order NGS for a patient with squamous NSCLC, because it isn’t rich with targetable mutations.

NGS is rich with information, including targetable mutations and novel mutations that I can sometimes refer to clinical trials. I also get information about TMB, and I can see genomic signatures, such as ultraviolet damage or microsatellite instability. All these things can be seen within an NGS panel.

The movement is toward the use of an NGS panel alone. We need to recognize that each panel can be slightly different. The NGS panel is rich with the most data and, therefore, has become the standard test. As the oncologist, I order it based on my knowledge of the patient’s stage of cancer, which we’ve not handed off to our pathologist at this point.

I put the wheels in motion in requesting NGS. Then we may have a discussion about the adequacy of the specimen, whether the tissue will work, and if not, we will need a new biopsy or a liquid biopsy to get the answer.

Dr Ritterhouse: Our approach is similar, but not the same. For all our patients with NSCLC, the pathologist originally puts in the request for the large, targeted NGS panel. Again, considering the turnaround time, all our oncologists agreed on this to increase our efficiency.

We also favor using 1 large NGS panel to look at all of the targetable biomarkers and to get additional information, such as TMB and microsatellite instability. This can all be done with 1 test. The only limitation is that in most institutions, the turnaround time for the larger panels is not quite what oncologists want.

Our turnaround time is 10 to 14 business days. We have agreed with our oncologists that we’ll also run a smaller targeted panel to get EGFR information sooner. We also do ALK and fluorescence in situ hybridization, although the information from both tests will eventually be on the large panel, but the oncologists want the information sooner. The turnaround time also influences what tests we order, and what oncologists are looking for. We’ve changed how many times we run tests to accommodate the time issue. Many times, if the targeted therapy information is not available, the oncologist and the patients are waiting for treatment, so we figure out what’s the best way to balance these issues.

Dr Oxnard: Indeed, there are periods when, as an oncologist, I say, “I can’t believe I’m still waiting for this test.” I’ve had instances when I’ve told the patient, “We’re not going to wait anymore. You need chemotherapy.” I ordered it, she had the infusion ready, and then the result came back showing she had a rare EGFR mutation, and I ran over and said, “Don’t get the chemotherapy. I’m going to order you a pill. It’ll be ready in a week.” We stopped the chemotherapy, and she went home. That’s the timing issue in oncology. We don’t trust that NGS is going to do that well with ALK and ROS mutations, so we’re using ALK IHC and ROS IHC fusions.

OPM: How do you use the TMB information?

Dr Oxnard: TMB is a newer biomarker. We combine it with the other biomarkers to get a sense of whether this patient is likely to benefit from a targetable therapy or from immunotherapy. If the patient has high PD-L1 expression, but low mutational burden and is a light smoker, I worry whether the PD-L1 is going to be associated with dramatic sensitivity. If the patient has low PD-L1, but a dramatic TMB and is a smoker, I will give that person a shot. It’s increasingly complicated, with increasing data coming out about how to use these as orthogonal approaches. We have data, and we have to be more nimble about incorporating the data.

PD-L1 is a biomarker with FDA-approved therapies, whereas TMB is part of an NGS package, but has no FDA-approved treatment yet. But we’re finding more ways to work with it. For example, data in small-cell lung cancer show that if the TMB is higher, the chance of benefit from immunotherapy or combination immunotherapy is better. But I don’t think about TMB or small-cell lung cancer as routine yet. We’re increasingly trying to incorporate TMB into these key decision points to offer the best chance of dramatic immunotherapy benefits to any patient.

Dr Ritterhouse: TMB is tricky for a pathologist running a lab and trying to incorporate it, because there’s no standardization across labs and across testing platforms in how we calculate it and what panel we use. All the original data were on whole-exome sequencing, and virtually no one does that in a clinical setting. Molecular pathology has to get standardization across different labs, especially for oncologists who need to know if it’s the same test.

OPM: What has been your experience with liquid bio­psies in lung cancer with respect to biomarker testing?

Dr Oxnard: I’ve worked on developing liquid biopsies or testing plasma cell–free DNA, because tumor biopsies are inconvenient for the patient, they’re risky for the doctor, they cause delays, and they’re frustrating. They can also be inconvenient for the pathologist, when the specimen is too small, and it doesn’t work out.

There is an urgency to get answers back quicker and more efficiently. A study we did showed that in patients who had a blood test and a tumor biopsy, the blood test took on average 3 days, whereas a new tumor testing for resistance took on average 28 days. This is a dramatic difference for a patient with advanced lung cancer.

We’ve been using liquid biopsies increasingly as an early screening test for a key mutation. If it’s present, we can act on it. If it’s not present, we can’t trust the negative result, and we have to use a tissue biopsy. The sensitivity of liquid biopsies is not great—approximately 70% for advanced lung cancer. It’s certainly faster than a tissue biopsy, but if the result is negative, we proceed with tissue biopsy.

How to integrate that into our treatment paradigm is challenging, especially for a patient with newly diagnosed advanced cancer. The biopsy may be far away or small. I send a blood test, start treatment, and the plasma NGS may come back in a couple of weeks. If the patient’s treatment is working well, I may not need it. But if the treatment is not working well, I will have the genomic data as a backup plan, as an alternative to empiric initial therapy. This requires nimbleness for doctors to figure out how to build these diagnostics into their care plan, but it fits a need, because of the difficulties with tumor biopsies and the delays in getting NGS.

Dr Ritterhouse: In many cases, liquid biopsy could be very helpful, as Dr Oxnard said. Specimen inadequacy is common, especially in lung cancer biopsies. At our institution, a liquid biopsy is mostly used for looking for resistance mutations. This is a test that we send out. We haven’t offered it clinically yet. Occasionally, if no other material is available or if all the material has been used, the liquid biopsy could be used in the first-line setting.

Dr Oxnard: We are increasingly targeting EGFR resistance mutations that require specific therapies. Similarly, increasing data show that ALK resistance mutations lead to other therapies. There are also MET resistance mutations and RAS resistance mutations. Each of these are opportunities for realizing, “I need a new biopsy. If a blood test could get me this answer quicker, it’s good for all involved.”

It’s worth remembering that the mutations in the blood are not just tumor mutations. There are blood mutations that are the patient’s germline mutations. You can stumble on a BRCA mutation in your report, and it’s actually a germline mutation. There are also white-cell mutations, clonal hematopoiesis mutations, or p53 mutations that are age-related or chemotherapy-related in our white cells. They shed into the blood and pollute the DNA. A blood test is not a true biopsy, and it doesn’t replace tumor bio­psies. Liquid biopsy is a shortcut, but we need to take it with a grain of salt, because it is not tumor genotyping. There’s no tumor DNA. We use a mixed DNA, hoping to see what the tumor is by testing plasma DNA.

OPM: We know that tumors are heterogeneous. How can you be sure that the biopsy sample is representative of the tumor rather than of that small part that is biopsied?

Dr Oxnard: We know that in drug resistance, where heterogeneity is increasingly a problem, we can see instances where a blood test shows one thing, and another biopsy shows another thing, and yet another biopsy would show something else. This is heterogeneity. I don’t think it’s generally a good thing for the patient if we’re targeting something that is heterogeneous. The chances are that any benefit will be transient. The blood test could capture resistance mutations from a range of sites. It could show the complex variety of mutations we need to treat. However, that’s the potential and may not be a reality.

We use the blood test as an efficient shortcut and as an alternative. If that doesn’t work, we fall back on tumor biopsy. I discourage physicians, though, from getting a biopsy, and then if it doesn’t show what they want, getting a blood test. Because then you end up with 2 biopsies that show different things, which is not good for anyone.

A blood test is a shortcut, and it cuts the pathologist out of the equation. You send the DNA to the molecular pathologist. The biopsy becomes the end result if the blood test is not providing the details we need.

Dr Ritterhouse: As far as which specimen is tested, that probably differs among institutions. Sometimes the oncologist wants this specific lung biopsy from 2016 tested, whereas at our institution, most of the time we select the test. If there are multiple specimens to test, we try the primary resection and the recurrence. Often, oncologists are more interested in the most recent specimen or the recurrence. We work with them to make sure that if we are testing tissue, we’re testing the most recent sample that may be applicable to whatever is going on for the current management.

Dr Oxnard: Some pathologists are interested in testing the biggest or most reliable specimens. You order testing for resistance, and the pathologist will say, “Oh, I’ve got this much better specimen from 2 years ago.” And then you are given a result on the whole specimen, which requires some details on what you’re looking for.

I also order a biopsy for EGFR resistance, and I’m just looking for a simple answer from the genetic testing. The pathologist will say, “Oh, this must be a new primary.” They do all these tests, and they get in the wrong direction, thinking they’re working up the wrong things. When you order these tests, you have to write down what you’re looking for—communicate and you can get the right test done.

Dr Ritterhouse: I love to get the order requisitions with notes from the oncologist, saying, “I’m looking for this, I’m interested in this.” It is very clear, and we can make sure we test the right thing from the very beginning, instead of generating a report and then being told, “This is not what we wanted. Please do it again.”

Dr Oxnard: The problem is that sometimes I order the biopsy, and then the intervention radiologist writes the pathology requisition. I may put a lot of data in my biopsy order, but that doesn’t get communicated with the pathology order. We have to acknowledge that we need to find ways to get the message directly to the pathologists who are handling the specimens.

Dr Ritterhouse: Yes, that can also be an issue if there are many members of the care team; it could be a nurse practitioner or a clinic coordinator who is placing the orders. Sometimes they may not be communicating the same results that the oncologist wanted. Getting everyone on the same page can be trickier than it sounds.

OPM: How do you streamline that process? What are the best practices?

Dr Oxnard: The best practices are evolving. The tricks that I’m learning as an oncologist are, if there is urgency, make sure the proceduralist and the surgeon or the radiologist know that I need that done quickly. We need to improve the communication. Sometimes the patient doesn’t realize the urgency, and the patient is scheduled for a visit in 2 weeks, but I need to see him or her tomorrow.

Communicate the urgency to the pathologist. When you order the biopsy, send a note at the same time to your thoracic pathologist, saying, “I’m getting this for resistance testing. Please, as soon as you get the specimen, cut the slides and send it to molecular testing.”

Molecular testing is what’s important. Don’t spend too much time on IHC and diagnosis. Biopsies take extra time, which is why they are frustrating, but are worth it.

The final thing you can do is recommend a fine-needle aspiration and a cytology specimen with each core biopsy that can be tested very quickly.

Dr Ritterhouse: The cytology specimens also have the benefit of timing the actual biopsy. There’s a cytopathologist who can immediately look at the slide and say whether this will be fine for molecular testing. The adequacy is assessed immediately, unlike in the core biopsy, where it can take 3 days for the pathologist to determine if it is adequate. The turnaround time of the whole process is too long. Molecular testing has improved the turnaround time.

OPM: What are the financial constraints to molecular biomarker testing for the treating physician, the pathologist, and the patient? And what is the reimbursement environment for biomarker testing?

Dr Ritterhouse: The reimbursement landscape for molecular testing causes considerable anxiety for molecular pathology lab directors. For the most part, we are well-reimbursed for the work we do for our patients with lung cancer. That’s one of the solid tumors that’s been at the forefront of precision medicine and targeted therapies, so that’s better understood and reimbursed by insurance companies.

In other tumor types, whether they get reimbursed varies. It’s also an issue in an academic hospital setting—it’s hard to know how many of the, say, 100 tests we do in 2 weeks actually get reimbursed. We try to get that information, but we can’t get that, because the hospitals are paid in a lump sum, and a fraction of that goes to all the clinical laboratories. We also don’t have feedback on our reimbursement on a per-test basis.

The best feedback we get is if we get an angry e-mail from an oncologist who got an angry phone call from a patient who had received a very large molecular testing bill. We’re fortunate that for our particular payer mix and population, that doesn’t happen too often. In those few cases, we try to work with the billing and finance departments to address those issues. Recently, certain insurance companies require preauthorization of all molecular tests. Some will require preauthorization for all molecular tests, including those that have been in use for more than a decade and are very cheap.

Dr Oxnard: Including for HER2 in breast cancer?

Dr Ritterhouse: Every test that my laboratory performs is under some insurance company’s requirements for preauthorization. This includes tests for patients who have a bone marrow transplant and need to be monitored every 2 weeks for a long time—that, too, falls under pre­authorization. Most institutions don’t have a great system for preauthorization for genetic testing. Our radiology colleagues know the patient is going to come in and get an MRI on a certain date. That’s the date of service, which means we can get the preauthorization completed before the patient comes in for the MRI or x-ray.

For a molecular test, the date of service—depending on whether it meets the new 14-day rule—can be when the specimen is obtained. The preauthorization is supposed to be done before the specimen is obtained, which is not physically possible in the molecular pathology setting. We’ve spent a lot of time trying to talk to payers to get a sense of how they envision this, and how this is going to be practically executed, because our turnaround times are already pushing the maximum of what’s acceptable for patient care.

Preauthorization can take a month, depending on the situation, which is unacceptable for patient care.

Dr Oxnard: We’ve had to meet with our local payers to come up with guidelines and consensus. We have some systems that enable us to acknowledge each time we ordered an NGS that it conforms to certain specifications.

The coverage determination has some constraints on how often we could order NGS. But this is not the reality for lung cancer. The reality is that lung cancer develops resistance, and patients have multiple primary lung cancers, so NGS is much more useful than a one-time test, but if we’re ordering it every month, that’s too much.

What is the cost for NGS? It costs less than 1 month of many of our modern therapeutics. Sometimes we get too concerned about the exact cost.

OPM: Overall, what do you consider the greatest challenges to biomarker testing today? How does your practice or hospital overcome these challenges?

Dr Oxnard: For me, the biggest challenge remains the tumor tissue. It’s the infrastructure that is needed to keep track of these specimens, and to have a team to handle them all. It’s getting more and more complex.

We need to invest in infrastructure to be able to get them and handle them. I think some centers or some physicians are giving up on testing and start empiric therapy. But we moved into precision therapy, and maybe we’re going to move away from it. It’s getting too hard. But we can’t allow that to be our practice. This is impor­tant for patients. The ability to embark on a tolerable therapy with high likelihood of benefits is so good for the patient that we cannot give up on precision therapy.

There are more and more drugs, and more and more biomarkers. The complexity is increasing, and it requires education and being informed. It’s hard, and it’s worth it. It’s not going to get easier. Maybe our molecular pathologists can make it easier on us. Maybe there are ways that we can have easier results, if only some of these reports would be simplified. That probably is something that we can start to do.

Just simplifying things for physicians to say, “Don’t make it complicated. Help me help the patient.” I’m not sure every company that generates reports appreciates these challenges that oncologists face daily.

OPM: When you simplify the report on the biomarker testing, this would suggest using a specific drug?

Dr Oxnard: By simplify, I mean that sometimes there are excess details, excess minutiae, or excess markers on the report that are confusing. How many of a 400-gene NGS panel actually affect the patient—maybe 12? The rest are just there to confuse us. Oncologists need to tell us about what they need. Community oncologists need to tell us what’s frustrating them. We can still make progress to make it easier for all involved to give good, precise cancer care.

OPM: Foundation medicine, for example, provides a report that says, “Here’s what we found. Here’s what you should be treating with.” Is this what community oncologists need? I know in academic centers you probably don’t need that, but community oncologists need that.

Dr Oxnard: Some results will tell us that this is a reliable and very targetable driver, and these drugs are available. Here is this fascinating other mutation, and you can think about this clinical trial. The oncologist will then ask me, “Well, that’s interesting. Should I do the trial or the reliable US Food and Drug Administration (FDA)-approved drug?” Take the FDA-approved drugs, for example. This was added just to make the report more interesting. That other stuff, we need to tone that down and focus on what is on-label therapy. Focus on the highlights and skip the other information, which is confusing for the patient and for the oncologist.

Dr Ritterhouse: That’s very helpful feedback. You get molecular pathologists and genetic counselors reviewing it, and they may go into the minutiae of this in-vitro study 10 years ago that showed that this variant might have this effect and that kind of thing. That’s not useful.

We generate the reports and we don’t always know how they are read or interpreted. Do they actually read my whole report? Do they just look at the list? These conversations are helpful for those who actually read the reports, whether they are community oncologists or your colleagues in an academic setting.

What do they want out of the report? How much are they not getting? We’ve even had conversations about trying to move it into our EMR to be more like a chemistry value. If you’re following EGFR mutations or resistance mutations, there should be a molecular tab. You should be able to have a list saying this day had this variant, something that’s not buried in the EMR and that’s easy to find.

OPM: At my hospital, the oncologists like to share these reports with the patient. If the oncologist is confused, you can only imagine what the patient thinks. Do your patients get copies of these reports, or do they have access to these reports?

Dr Oxnard: Patients can get the reports. They don’t always prioritize that, but the motivated patient or an anxious patient may pore over every finding, and it can slow you down. Patients don’t appreciate information saying they have EGFR mutation or resistance. They say, “Should we check for ROS mutation now?” It doesn’t work like that. You either have EGFR mutation or a ROS mutation.

I can envision a day when oncologists will say, this is frustrating me and slowing me down. It’s just leading to negative testing. I don’t want us to get there, but I think we need to be sensitive to the burden we’re putting on clinicians with these reports, and how to make them more efficient so they can help us give good care.

OPM: This interview will be read by many oncologists in different cancer centers, and many of them are community-based. What are best practices that cancer practices could adopt regarding optimizing biomarker testing?

Dr Oxnard: As an oncologist who treats patients with lung cancer, I want every patient I see to be genotyped. I want them to be characterized and tested. I keep track of whether they have EGFR mutation, KRAS mutation, or no mutation. A patient who gets ill and dies without testing has missed out on opportunities.

We need to make sure that every patient today gets an opportunity at molecular testing to find what drugs will work best. If that requires you to start therapy while pursuing testing for the future, that’s really important. We need to make sure we have backup plans for our patients, and molecular testing allows us to do that. That’s the movement toward precision oncology that all of us need to adopt in our daily practice.

Dr Ritterhouse: I think best practices for pathologists, surgical pathologists, and molecular pathologists are to remember that we are not working in isolation, and we need to form very close working relationships with our clinical colleagues and the oncologists, to have open and frequent dialogues about the best way to take care of our patients.

What are the challenges that the oncologists are facing with getting the specimens or getting the report, digesting the report in an efficient manner, and working together to improve small things? Many of the best changes that we’ve had at our institution have come from these multidisciplinary efforts of increasing specimen adequacy and reducing turnaround time.

It’s important to reach out to all your colleagues in different departments and figure out a way to move things forward and make things better.

OPM: That’s very helpful. Thank you both for this very informative discussion.

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